Mouse vomeronasal organ decodes cat threat

Mice are genuinely fearful of cats; and when they encounter the aroma of a feline, they freeze and then scarper. This happens thanks to an accessory smell system called the vomeronasal organ, or VNO. One of its roles is to detect pheromones, and its wiring into the limbic system enables it to coordinate mating behaviours. But it can also detect predator smells, including cats, and projections to the hypothalamus initiate defensive responses. Interestingly, the extent of these responses is not binary; they’re proportional to the intensity of the stimulus. Speaking with Chris Smith, Sachiko Haga-Yamanaka, from the University of California, Riverside, has used cat tears, which contain odourants that the mouse VNO is sensitive to, to unpick the neurological pathways responsible…

Sachiko - What we are looking at is inter-species communications. The vomeronasal organ or VNO can detect chemical cues from predator species in prey animals. So what we are looking at is how the predators can control the behaviour of the prey animals.

Chris - Where is the vomeronasal organ located?

Sachiko - The vomeronasal organ is situated within the nasal cavity between the nasal cavity and oral cavity.

Chris - Is it therefore anatomically distinct from the bits of the olfactory system that smell other smells? For instance, if I bury my nose in, in a bunch of flowers, if I were a mouse and I was sniffing flowers, I would smell the flower scent with one part of my system, but I would smell other things with this vomeronasal organ. It's a separate entity from the, the rest of the olfactory system?

Sachiko - Yeah, exactly. The vomeronasal organ is sensory organ of the accessory olfactory system, and then the main smell is detected through the main olfactory system.

Chris - And how is it wired up? What's it connected to and what supplies the, the innovation to carry signals from it and to where?

Sachiko - The vomeronasal organ contains sensory neurons and then the axons of the sensory neurons travel to the frontal part of the brain called the accessory olfactory valve. And then from there, send the signal to the amygdala or the hypothalamus that controls innate behaviour such as mating or defensive behaviour.

Chris - How did you use that understanding then to test whether or not it could detect, for instance, the, the smell and presence of a potential predator?

Sachiko - First of all, we looked at the behaviour to the, the source of the predator acute. In our case, cat saliva was used as a predator acute source. And then we looked at the behaviour changes. At the same time, we also looked at whether the sensory neurons in the vomeronasal organ was activated or not using the specific neural activity marker called the c-fos.

Chris - Right. So in other words, you can present the, the cat saliva, which you, which you hypothesise. The mouse can smell and be alarmed by. And you are looking to see if, when that is present, the nerves that connect between the vomeronasal organ and relevant brain target structures, whether they change their activity, which would argue they are sensing the smell of the cat saliva?

Sachiko - Yes.

Chris - So, that tells you they're sensitive to it, but how do you probe what it does to their behaviour?

Sachiko - What we looked at was freezing behaviour. The freezing is one type of the defensive behaviour response.

Chris - So, if I present some, some of the particular odor to the mouse, it will, it will freeze when it smells it. That's what you're saying, isn't it? It will, it will suddenly lock up?

Sachiko - Yes. Lock up, yes.

Chris - Once you establish that that scent is detected and it's going to these different brain areas, how did you then try to establish how the response is programmed?

Sachiko - At the specific population of the neurons in the hypothalamus are activated by cat saliva exposure, and then the activation controls the freezing behaviour output.

Chris - And is it a proportional response? So if I had a big dollop of cat saliva, would I get a bigger response or is it a binary thing? It's all or nothing.

Sachiko - Yeah. We tested that regular amount of the cat saliva and the diluted cat saliva. The non-diluted cat saliva induce robust behaviours, but diluted, like almost diminish the freezing behaviour response.

Chris - So it does mean that the animals can make a proportionate response to ovarian concentration of the potential threat stimulus from the environment?

Sachiko - Exactly.

Chris - What have we learned then? If you could sum up, if you were to give us a summary of what this study adds or how this changes our understanding. What do you think you've done to move the field forward with this?

Sachiko - What we found was that data queue contained a time-sensitive component that influenced the intensity of the defensive behaviour output. And then the VNO can detect such time sensitive chemical cues and then the moderate, the intensity of the behaviour through the VNO mediated neuro circuitry. The ventral medial hypothalamus is involved in the circuitry and regulates defensive behaviour outputs.